title: Complications associated with the administration of dantrolene 1987 to 2006: a report from the North American Malignant Hyperthermia Registry of the Malignant Hyperthermia Association of the United States.
abstract: BACKGROUND
  Dantrolene is the only specific treatment for malignant hyperthermia (MH), a genetic disorder in which life-threatening temperature increase has been induced by inhalation anesthetics and succinylcholine. Because MH presents with nonspecific signs and delay of treatment can be fatal, dantrolene may be given as soon as MH is suspected. We report the complications associated with dantrolene administration as documented in AMRA (adverse metabolic/musculoskeletal reaction to anesthesia) reports submitted to the North American Malignant Hyperthermia Registry.
  
  
  METHODS
  AMRA reports were analyzed for differences between subjects with and without complications attributed to dantrolene. Documentation of dantrolene dose and subject weight were inclusion criteria. Because some reported complications were likely due to factors other than dantrolene, a reduced set of cases was also defined. We used χ(2) and Mann-Whitney tests. Logistic regression was applied to describe factors associated with increased risk of complications.
  
  
  RESULTS
  In the full dataset of 368 subjects, the most frequent complications associated with dantrolene were muscle weakness (21.7%), phlebitis (9%), gastrointestinal upset (4.1%), and respiratory failure (3.8%). Logistic regression described a 29% increase in risk of any complication when the total dantrolene dose was doubled, a 144% increase in risk when fluid administration was part of treatment, an 83% decrease in risk in the presence of neurosurgery, and a 74% decrease in risk in the presence of oral surgery. In the dataset reduced by removal of some serious complications that were judged likely to have been due to preexisting disease or the MH event, there were 349 subjects. The most frequent complications associated with dantrolene were muscle weakness (14.6%), phlebitis (9.2%), and gastrointestinal upset (4.3%). In this reduced dataset, logistic regression described a 25% increase in risk of any complication when the total dantrolene dose was doubled, a 572% increase in risk in the presence of obstetric or gynecologic surgery, a 56% decrease in risk if furosemide was given, and no relationship with fluid administration or other types of surgery.
  
  
  CONCLUSIONS
  Complications after dantrolene are common, but rarely life threatening. Unidentified factors in the surgical environment are associated with changes in the risk of complications. Fluid management, as part of the treatment of MH, has an important association with the risk of complications after dantrolene administration and should be monitored closely.
authors.affiliation: The North American Malignant Hyperthermia Registry of MHAUS, 1400 Locust Street, Room 8522-3, Ermire Building (B), Eighth Floor, Pittsburgh, PA 15219, USA. BrandomBW@anes.upmc.edu
authors.forename: Barbara W
authors.initials: BW
authors.lastname: Brandom
authors.forename: Marilyn Green
authors.initials: MG
authors.lastname: Larach
authors.forename: Min-Shue Alvin
authors.initials: MS
authors.lastname: Chen
authors.forename: Michael C
authors.initials: MC
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001835:Body Weight; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003620:Dantrolene / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005440:Fluid Therapy / Q000009:adverse effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D008305:Malignant Hyperthermia / Q000175:diagnosis / Q000188:drug therapy*; D008875:Middle Aged; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000009:adverse effects*; D009656:North America; D016017:Odds Ratio; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D012955:Societies, Medical; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009125:Muscle Relaxants, Central; D003620:Dantrolene